Project Summary Here we request funds to purchase an upright Nikon A1R-MP multiphoton microscopy system with a high-resolution galvanometer-based scanner, a high-speed resonant scanner, a femtosecond infrared pulse laser (700-1080 nm), three GaAsP detectors, and a high sensitivity extended red response PMT. The instrument will be housed within the UW-Madison Optical Imaging Core (UWOIC) facility at the University of Wisconsin- Madison. The goal of this facility is to provide access to a range of optical imaging modalities to all research groups on campus, with an emphasis on high speed, high- resolution microscopy. Importantly, we have outfitted our facility with a full tissue culture suite, with space for animal housing available on a nearby floor, to enable users from anywhere on campus to use instruments here. The multiphoton system will be the first of its kind in any imaging core facility on the UW-Madison campus and will fill a critical void in available technologies to UW investigators. It will immediately serve more than twenty NIH funded research laboratories, with expertise in metabolism, neuroscience, regenerative medicine, oncology, biomaterials, and immunology. As the user base of the core facility continues to grow (more than 150 individuals conduct work here), we have observed a dramatically increased demand for deep tissue imaging, which cannot be satisfied by the single photon confocal systems currently available on campus. In response, we have partnered with the UW-Madison School of Medicine and Public Health, the UW Carbone Cancer Center, and the Office of the Vice Chancellor for Research and Graduate Education and identified matching financial support for this application to purchase a state-of-the-art multiphoton microscopy system. Committed long-term funds will also fully support a full time core manager and an extended service contract for the Nikon A1R-MP system. We anticipate that the addition of this multiphoton microscope will not only greatly strengthen current NIH-funded projects, but will also allow our users to explore new questions not previously tenable in the absence of a platform to image deep into samples with high speed. Therefore, this instrument will play a critical role in promoting new discoveries in basic and clinically relevant sciences and will support cutting edge projects into the foreseeable future.